2025-08-29 北京大学(PKU)
<関連情報>
- https://newsen.pku.edu.cn/news_events/news/research/15074.html
- https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00263-2
低血糖症に対する生体内保護能を有する内分泌サブタイプ完全ヒト多能性幹細胞由来膵島細胞の再構築 Reconstruction of endocrine subtype-complete human pluripotent stem cell-derived islets with capacity for hypoglycemia protection in vivo
Gaofan Meng ∙ Jiabin Gu, ∙ Soon Yi Liew ∙ … ∙ Yuanyuan He ∙ Cheng Li ∙ Hongkui Deng
Cell Stem Cell Published:August 8, 2025
DOI:https://doi.org/10.1016/j.stem.2025.07.006
Graphical abstract
Highlights
- Reconstruction of pluripotent stem cell-islets comprised all five endocrine subtypes
- Transplantation of these islets recapitulated bidirectional glycemic modulation
- Hypoglycemic protection was enhanced by balancing β and non-β endocrine composition
- Defective counterregulatory response was restored in diabetic mice recipients
Summary
Transplantation of pluripotent stem cell-derived islets (PSC-islets), containing functional insulin-producing β cells, represents promising cell therapy for restoring glycemic control in diabetes. However, recapitulation of complete endocrine composition in PSC-islets remains challenging, and their ability to counteract hazardous hypoglycemia, crucial to metabolic safety in vivo, remains unexplored. Here, we report robust generation of non-β cells in vitro. By incorporating non-β and β cells, we report reconstruction of PSC-islets comprising all five (α, β, δ, ε, and γ) endocrine subtypes (reconstructed PSC-islets). After reversal of hyperglycemia in diabetic mouse models, these islets exhibited robust protection against hypoglycemia, with only 3% of measurements falling below 54 mg/dL compared with 59% in non-reconstructed controls. Remarkably, hypoglycemic clamp assays suggested restoration of previously defective counterregulatory response in reconstructed PSC-islet recipients. These findings establish a strategy to control relative abundance of PSC-islet subtypes, providing a basis for calibrating post-transplant glycemic homeostasis with definitive hypoglycemic protection.
